Novel prepolymers useful in biomedical devices

ABSTRACT

A novel polyurethane based prepolymer useful in biomedical devices which provides high oxygen permeability and superior physical properties.

FIELD OF THE INVENTION

The invention relates to specific prepolymers especially useful asmonomers that can be formed into biomedical devices.

BACKGROUND OF THE INVENTION

Heretofore, biomedical materials especially useful commercially ascontact lenses have been based upon polymers and/or copolymers of aselect set of chemistries. Methylmethacrylic acid type chemistries formthe oldest type, the polymers from which poly(methylmethacrylates)(PMMA) have been surpassed by hydrogel chemistries based uponpoly(hydroxyethyl methacrylate) (pHEMA) or polyvinyl pyrrolidinone(pNVP), and copolymers of HEMA and NVP. These materials formed the basisfor most soft contact lenses.

Silicone chemistries have played a lesser role in the marketplace, buthave offered higher oxygen permeabilities than their hydrogelcounterparts. They have, however, presented certain performancecharacteristics which limit their application—specifically surfacewettability problems.

Copolymers employing PMMA types of chemistry have been employed inconjunction with silicone chemistry and hydrogel chemistry to produce awide assortment of materials which have the common characteristics ofhigh oxygen permeability and high modulus (rigidity). These materialshave been characterized as hard gas permeable or rigid gas permeablematerials.

Urethane chemistries have not been employed commercially in the contactlens market despite significant work in the area such as U.S. Pat. No.3,786,034 issued to Blair et al relates to hard, hydrophilicpolyurethane material formed from reacting a specific polyol with apolyfunctional isocyanate. U.S. Pat. No. 3,821,186 teaches similarmaterials as U.S. Pat. No. 3,786,034.

U.S. Pat. No. 4,136,250 teaches a polymer formed by reacting a highmolecular weight polydimethyl siloxane diol with 2 mole equivalentsisophorone diisocyanate and then reacting with excess hydroxy containingmonomers. Essentially, this is a soft segment prepolymer endcapped withethylenically reactive endcap. These materials are relatively weak andin their hydrated form show low degrees of elongation.

U.S. Pat. No. 4,309,526 teaches adhesive compositions which employ lowmolecular weight polyols reacted with diisocyanates and short chaincycloaliphatic or aromatic diols, endcapped with hydrophilic endcaps.Various characteristics such as oxygen permeability are not mentioned.

U.S. Pat. No. 4,359,553 teaches polyurethane diacrylate compositionsuseful as biomedical materials which are formed by reacting a diol mw200 to 20,000 with 2 mole equivalents diisocyanate which is then reachedwith diethyleneglycol diacrylate to form the water soluble polyurethane.Specific applications taught in the patent are as controlled releasematrices.

U.S. Pat. No. 4,454,309 teaches a hydrophilic random block copolymerwith polyurethane linkage between randomly using high molecular weightpolyols and low molecular weight ethylene mers. The materials absorbed100-500% by weight additional water.

U.S. Pat. No. 4,740,533 teaches materials which are block copolymers ofpolyoxyalkylenes and polysiloxanes which have no hard segments.

U.S. Pat. No. 4,780,488 teaches a prepolymer with only a central softsegment endcapped with hydroxyethyl methacrylate endcaps or the like.

The art does not disclose polyurethane prepolymers useful as biomedicalmaterials with the hard-soft-hard or the soft-hard-soft configurationsdisclosed herein which are oxygen permeable and still exhibit exemplaryphysical strength characteristics. Nor does the art teach that theseprepolymers are useful as biomedical materials.

SUMMARY OF THE INVENTION

The present invention relates to prepolymers especially useful inbiomedical copolymers of the general formula:E(*D*A*D*G)_(a)*D*A*D*E′ orE(*D*G*D*A)_(a)*D*G*D*E′where

A denotes a divalent polymeric radical chosen from the group of

wherein

-   -   R^(P) denotes a straight or branched alkyl group with 1 to 6        carbon atoms and n provides for a moiety weight of the radical        between 2000 and 10,000;    -   R^(F) denotes a fluorinated straight or branched alkyl radical        with 1 to 6 carbon atoms and m provides a moiety weight of        between 400 and 10,000;    -   R^(S) denotes an alkyl radical or a short chain fluorinated        alkyl radical with 1 to 3 carbon atoms; and    -   p provides a moiety weight of 400 to 10,000;

-   D denotes an alkyl diradical, an alkyl cycloalkyl diradical, a    cycloalkyl diradical, an alkylaryl diradical or an aryl diradical,    with 6 to 30 carbon atoms;

-   G denotes an alkyl diradical, a cycloalkyl diradical, an alkyl    cycloalkyl diradical, an aromatic diradical or an alkylaromatic    diradical with 1 to 40 carbon atoms which may have ether, thio, or    amine linkages in the main chain;

-   * denotes a urethane or ureido linkage; and

-   E and E′ denote polymerizable unsaturated organic radicals    represented by the general chemical formula    wherein    -   R¹ denotes a divalent alkylene radical with 1 to 10 carbon        atoms;    -   R² denotes a —H or —CH₃ radical;    -   R³ denotes a —H radical or an alkyl radical with 1 to 6 carbon        atoms or a        radical where    -   Y is —O—, —S— or —NH— and R⁴ denotes an alkyl radical with 1 to        12 carbon atoms;    -   X denotes    -   Ar denotes an aromatic radical with 6 to 30 carbon atoms;    -   a is at least 1;    -   w is 0 to 6;    -   x is 0 or 1;    -   y is 0 or 1; and    -   z is 0 or 1.

These prepolymers are especially useful in forming copolymerizates withethylenically unsaturated monomers which are known and used in thebiomedical materials field. The resultant copolymers have a combinationof oxygen permeability, surface wettability and physical strength in dryand/or hydrated forms otherwise unavailable.

DETAILED DESCRIPTION OF THE INVENTION

The prepolymers of the present invention are especially useful in makingbiomedical materials due to this combination of physical strength andhigh oxygen permeability when copolymerized with state of the artethylenically unsaturated biomedical monomers. The combination ofadvantageous properties is achieved due to the specific chemistryinherent in the claimed prepolymer.

The prepolymers of the invention can be represented by the generalformulae:E(*D*A*D*G)_(a)*D*A*D*E′ orE(*D*G*D*A)_(a)*D*G*D*E′where

A denotes a divalent polymeric radical chosen from the group of

wherein

-   -   R^(P) denotes a straight or branched alkyl group with 1 to 6        carbon atoms and n provides for a moiety weight of the radical        between 2000 and 10,000;    -   R^(F) denotes a fluorinated straight or branched alkyl radical        with 1 to 6 carbon atoms and m provides a moiety weight of        between 400 and 10,000;    -   R^(S) denotes an alkyl radical or a short chain fluorinated        alkyl radical with 1 to 3 carbon atoms; and    -   p provides a moiety weight of 400 to 10,000;

-   D denotes an alkyl diradical, an alkyl cycloalkyl diradical, a    cycloalkyl diradical, an alkylaryl diradical or an aryl diradical,    with 6 to 30 carbon atoms;

-   G denotes an alkyl diradical, a cycloalkyl diradical, an alkyl    cycloalkyl diradical, an aromatic diradical or an alkylaromatic    diradical with 1 to 40 carbon atoms which may have ether, thio, or    amine linkages in the main chain;

-   * denotes a urethane or ureido linkage; and

-   E and E′ denote polymerizable unsaturated organic radicals    represented by the general chemical formula    wherein    -   R¹ denotes a divalent alkylene radical with 1 to 10 carbon        atoms;    -   R² denotes a —H or —CH₃ radical;    -   R³ denotes a —H radical or an alkyl radical with 1 to 6 carbon        atoms or a        radical where    -   Y is —O—, —S— or —NH— and R⁴ denotes an alkyl radical with 1 to        12 carbon atoms;    -   X denotes    -   Ar denotes an aromatic radical with 6 to 30 carbon atoms;    -   a is at least 1;    -   w is 0 to 6;    -   x is 0 or 1;    -   y is 0 or 1; and    -   z is 0 or 1.

The prepolymers upon polymerization form two domains which can becharacterized as hard and soft domains, respectively. The soft domaingenerally have glass transition temperatures (Tg s) lower than roomtemperature whereas the hard domains have Tg s higher than roomtemperature. Upon polymerization, the hard segments of the prepolymerassociate with one another and the soft segments form the soft domainwhich account for the oxygen permeability of the polymeric mass. Thecombination of hard and soft segments provides the polymer with superiormechanical properties otherwise unavailable.

The hard segments of the prepolymer are formed by the reaction of theshort chain diol with the diisocyanate. Thus, in the formulae supra, the“hard segments” are represented by the *D*G*D* portions of the formulae.Thus termed, formula (i) represents a hard-soft-hard prepolymer andformula (ii) represents a soft-hard-soft prepolymer.

The isocyanates which can be used in preparation of the inventioninclude, toluene diisocyanate, 4,4′-diphenyl diisocyanate,4,4′-diphenylene methane diisocyanate, p-phenylene diisocyanate,dianisidine diisocyanate, 1,5 napthalene diisocyanate, 4,4′-diphenylether diisocyanate, 4,4′(dicyclohexyl)methane diisocyanate,1,3-bis-(isocyanato methyl)cyclohexane, cyclohexane diisocyanato,tetrachlorophenylene diisocyanate, isophorone diisocyanate, and3,5-diethyl-4,4′-diisocyanato diphenyl methane.

Other diisocyanates which may be used are higher molecular weightdiisocyanate formed by reacting polyamines which are terminally cappedwith primary or secondary amines, or polyhydric alcohols with excess ofany of the above described diisocyanates. In general, these highmolecular weight diisocyanates will have the general formula

wherein R is a divalent organic radical with 2 to about 20 carbon atoms,X is —O—, or —NR′—, where R is —H or a lower alkyl, and B is a divalentorganic radical.

The diisocyanate is reacted with low molecular weight diols or glycolssuch as 2,2-(4,4′ dihydroxydiphenyl)-propane (bisphenol-A),4,4′-iso-propylidine dicyclohexanol (hydrogenated biphenol-A),ethoxylated bisphenol-A, propoxylated bisphenol-A,2,2-(4,4′-dihydroxydiphenyl)-pentane,α,α′-(4,4′-dihydroxydiphenyl)-p-diisopropyl benzene, 1,3 cyclohexanediol, 1,4-cyclohexane diol-1,4-cyclohexane dimethanol, bicyclic andtricyclic diols such as 4,8-bis-(hydroxymethyl)-tricyclo [5.2.1.0^(2,6)]decane, neopentyl glycol, 1, 4 butanediol, 1,3-propanediol,1,5-pentanediol, diethylene glycol, triethylene glycol and the like.

These hard segments as mentioned before form hard domains in the finalpolymer or copolymer by association via hydrogen bonding with otherrigid segments. The degree of association within the hard domain can bemodified by controlling the amount of hydrogen bonding between thesegments by either 1) decreasing the overall weight content of the hardsegment in the prepolymer by increasing the molecular weight of the softsegment or 2) by decreasing the amount of hydrogen bonding density inthe hard segment by either using relatively soft, longer chained diols,or by using primary amines or secondary amines capped low molecularweight compounds in conjunction with the diisocyanates rather than thediols.

The hard segments are then reacted with a relatively high molecularweight polymer which is α,ω-endcapped with two active hydrogens, usuallyhydroxyl groups. These segments form the so-called soft segment of theprepolymer. Various types of high molecular weight polymers can be usedincluding in general polymers of the following formulae

Formulae a) represents polyoxyalkyleneglycols which are generallycommercially available in the molecular weight range called for in thepresent invention. These diols include polymers prepared from theepoxides: ethylene oxide 1,2-propylene oxide, 1,2-butylene oxide, 2,2epoxydecane, 1,2-epoxyoctane, 2,3-epoxy norborane, 1,2-epoxy-3-ethoxypropane, 2,2-epoxy-3-phenoxypropane, 2,3-epoxypropyl-4-methoxy phenylether, tetrahydrofluran, 1,2-epoxy-3-cyclohexyloxy propane, oxetane,1,2-epoxy-5-hexene, 1,2-epoxyethylbenzene,1,2-epoxy-1-methoxy-2-methylpropane, benzyloxy propylene oxide, the likeand combinations thereof.

The preferred polymers of this class are polypropylene glycols ofmolecular weights, 2000, 3000 and 4000 and more and polyoxyethylenepolyoxypropylene block copolymers with molecular weight greater than2000.

Formulae b) represents polyfluoroethers with α,ω-active hydrogens. Thisclass of polymers can be synthesized per the heading of U.S. Pat. No.3,810,874. Generally, these polymers should have molecular weightsbetween 400 and 10,000 to be useful in the present invention.

Formulae c) represents a α,ω-dihydroxyl alkyl endblocked polysiloxanewhich for the purpose of the present invention should have a molecularweight in the range of 400 to 10,000. These polysiloxanes can besynthesized by reacting a disiloxane of the general formula

with cyclopolydimethyl siloxane under acidic conditions.

Alternately, the disiloxane can be replaced with dimethoxydimethylsilaneor diethoxy dimethyl silane to produce the α,-ωdihydroxy endcappedpolysiloxanes.

The endcapping monomers used in the prepolymer are generally representedby the formula

as defined supra. The Stage B reaction product is reacted with an excessof suitable acrylate or methacrylate esters containing a hydroxy oramine group on the non-acrylate or non-methacrylate portion of themonomer to form the endcaps of the above formula. Suitable endcapmonomers include hydroxyethyl acrylate, hydroxyethyl methacrylate,aminoethyl methacrylate, 3 hydroxypropyl methacrylate, amino propylmethacrylate, hydroxyhexylacrylate, t-butylaminoethyl methacrylate,monoacrylate or monomethacrylate esters of bisphenol-A and/orbisphenol-B.

General Synthetic Approaches

The prepolymers of the present invention are formed by two generalsynthetic approaches. One approach produces the hard-soft-hardprepolymer while the second approach produces the soft-hard-softprepolymer. Variations of each scheme were found to be necessary forspecific rigid/soft segment combinations, details of which are disclosedin the examples.

Hard-Soft-Hard Prepolymer Synthetic Schemes

The scheme used to produce this type of prepolymer employed three stagesto produce the final prepolymer. The first stage (STAGE A) involvedreacting 2 mole equivalents of diisocyanate with about 1 mole equivalentlow molecular weight diols described herein. If these diols could berepresented by the symbol ▴G▴, where ▴ denotes a hydroxyl radical and Grepresents the rest of the diol compound, and the diisocyanatefunctional compound could be represented by ●D● where ● represents anisocyanate radical, the STAGE A reaction can be schematicallyrepresented as follows:2●D●+▴G▴→●D*G*D●where * denotes a urethane or a ureido linkage. STAGE A produces aso-called “Hard” segment. As is known to those skilled in polymerchemistry, the product ●D*G*D● is the mathematical average of allreaction product molecules. The reaction product of the actual reactionwill contain ●O● and ●D(*G*D)_(C)*G*D with c≧2. Again, the formulas arenumerical averages.

STAGE B involves reacting about one half mole equivalent of a α,ω-diolendcapped long chain polymer with the reaction product of STAGE A. If▴A▴ represents the long chain diol the STAGE B Reaction is

2●D*G*D●+▴A▴→[●D*G*D*]₂A

In STAGE C, the reaction product from STAGE B is reached with a molarexcess of an endcapping monomer which has: 1) hydroxyl or aminefunctionality; and 2) some polymerizable unsaturation. If the endcapperis represented by the symbol E▴, where is —OH or —NH₂ or —NH—, thereaction proceeds generally as[●D*G*D*]₂A+2E▴→[E*D*G*D*]₂A

Optionally, STAGE B can be run with molar excess of A to producemultiblock polymers of the general formula ●(D*G*D*A)_(a)*D*G*D● where ais at least 1. This reaction product would be endcapped in STAGE Cabove.

Soft-Hard-Soft Prepolymer Synthetic Scheme

The second general synthetic scheme using the same nomenclaturedescribed is represented by the following general formulae:2●D●+▴A▴→[●D*]₂A  STAGE A2[●D*]₂A+▴G▴→[●D*A*D*]₂G  STAGE B[●D*A*D*]₂G+2E▴→[E*D*A*D*]₂G  STAGE CIn general, each of the reaction stages is run until the reactive stepis complete. Reaction progress in STAGES A and B reactants weremonitored by acid base titration. The isocyanate content was calculatedby the difference of acid equivalents between a stock solutiondibutylamine and its reaction product with the diisocyanate reactionintermediate. The reaction was also monitored by ATR-IR for theappearance/disappearance of peaks at 1700 cm-¹, which indicated thepresence of

and 2250 cm-1 which indicated consumption of —N═C═O.

It was found that the synthesis of the prepolymer could be run neat orin solution. A wide range of aprotic solvents can be used to synthesizethe prepolymers of the present invention. Solvents useful in thesynthesis include toluene, methylene, chloride, benzene, cyclohexane,hexane, heptane and the like. Preferred solvents are toluene, methylenechloride and mixtures thereof.

Reaction of the prepolymer precursors may be accomplished in thepresence or absence of catalysts for urethane reactions, such catalystsbeing well known in the art. The first step of prepolymer synthesiswhere diisocyanate is first reacted with a short carbon chain (2 to 30carbon atoms) diol, particularly where an aromatic diisocyanate is used,proceeds very rapidly, even in the absence of any catalyst. In fact,during the step of reacting diisocyanate and short chain diol,temperature control may be required in order to avoid/minimize sidereactions.

Preferably, the first step of prepolymer synthesis in accordance withthe present invention is carried out below about 100° C., most suitablywithin the range of from about 60° C. to about 90° C. Thereafter, thesecond step of the reaction is carried out at comparable temperatures,preferably within the range of from about 40° C. to 70° C. The finalstep of prepolymer formation suitably is effected at temperatures offrom about room temperature to about 100° C., with a narrow range offrom about 40° C. to about 50° C. being most preferred. As will beapparent to those skilled in the art, optimal reaction conditions, suchas temperatures and duration, are selected for each individual reactionsystem to achieve conditions that produce a favorable rate of reactionwithout fostering undesirable side reactions.

Among the suitable catalysts for use in prepolymer formation are tinsalts and organic tin esters, such as dibutyl tin dilaurate, tertiaryamines, such as triethyl diamine and other recognized catalysts, such as1,4-diaza (2.2.2)-bicyclooctane (DABCO).

The prepolymers of the present invention are particularly useful ascomonomers with state of the art ethylenically reactive monomers usefulin the field of biomedical materials. In general, these monomers are thehydroxyalkyl acrylates and diacrylates such as hydroxyethyl acrylate,hydroxypropyl acrylate, and the corresponding methacrylate compounds,including cyclohexyl methacrylate, methyl methacrylate, isobornylmethacrylate, lauryl methacrylate, triethylene glycol dimethacrylate,isobuty methacrylate and tetrahydrofurfuryl methacrylate and otherunsaturated reactive monomers such as acrylamides, methacrylamides,pyrrolidinones, stryene and acrylonitrile can be used as well and othermonomers known in the art including fluorinated analogs of all of thepreviously mentioned monomers and the organo silicone comonomers knownin the art. Specific fluorocomonomers include:

-   (2,2,2-trifluoroethyl) itaconate-   (hexafluoroisopropyl) itaconate-   (1H, 1H-perfluorooctyl) itaconate-   (1H, 1H, 111H-perfluoroundecyl) itaconate-   (perfluoro-t butyl) itaconate-   (pentafluorophenyl) itaconate-   (2H, 2H-perfluorobenzyl) itaconate-   (pentafluorophenylmethyl) itaconate-   (decafluorocyclohexyl) itaconate-   (1H-perfluorocyclohexyl) methyl itaconate-   (1,1,1-trifluoroisopropyl) itaconate-   1-methyl-4-(hexafluoroisopropyl) monoitaconate-   4-(hexafluoroisopropyl) monoitaconate-   1-(1H, 1H-perfluorooctyl)-4-hexafluoroisopropyl) itaconate    and methacrylate analogs thereof.

Specific organosilicon comonomers include:

-   tris(2-acetoxyethyldimethylsiloxy)silylpropyl acrylate and    methacrylate-   tris(2-carboxyethyldimethylsiloxy)silylpropyl acrylate and    methacrylate-   tris(3-hydroxypropyldimethylsiloxy)silylpropyl acrylate and    methacrylate-   acrylate and methacrylate functional, fluorosubstituted alkyl/aryl    siloxanes such as:-   tris(3,3,3 trifluoropropyl dimethylsiloxy) silyl propyl acrylate and    methacrylate-   tris[3-heptafluoroisopropoxy propyl)] dimethysiloxy silylpropyl    acrylate and methacrylate-   tris(pentafluorophenyl dimethysiloxy)silyl propyl acrylate and    methacrylate

Other potentially useful organosilicon comonomers include:

-   p-(pentamethyldisiloxanyl) styrene-   bis(trimethylsiloxy)-   pyrrolidinonyldimethyl-   siloxy-silylpropyl acrylate and methacrylate.    When used as comonomers these materials can be used from 5 to 85    weight percent of the final copolymer weight with the balance    comprising the prepolymer portion.

Other di-ethylenically reactive monomers can also be used to effect themechanical and surface properties. Such crosslinks are generallyemployed in the 0.1 to 5 wt % range.

The polymers and copolymers are formed by a free radical mechanism usinga wide variety of known free radical catalysts such as the diacylperoxides such as benzoyl peroxide; dialkyl peroxides such as di-tert,-butyl peroxide; ketone peroxides such as methylethyl ketone peroxide;and peresters which readily hydrolyze, e.g. tert-butyl peracetate,tert-butyl perbenzoate, di-tert-butyl diperphthalate, etc. Aparticularly useful class of peroxy initiators are the organichydroperoxides such as cumene hydroperoxide, methylethyl ketonehydroperoxide, tert-butyl hydroperoxide, etc. The initiators should beused at a concentration of about 0.01 percent to about 10 percent byweight of the total formulation, preferably about 0.1 percent to about 5percent by weight. Another useful class of initiators comprisescarbonyl-containing ultraviolet-activated free radical generators, suchas acetophenone, benzophenone, and the benzoin ethers. Other suitable UVinitiators are known in the art. Initiator mixtures may also be used.

Solvents can be used in the final copolymerization and/or polymerizationprocess. Solvent choice will depend upon the solubility parameters ofthe prepolymer and of the comonomers used, if any, and should be chosento allow full solubilization of all polymerizate components.

In certain instances, the copolymerization process should be carried outwithout solvent. For instance, when 2-hydroxyethyl methacrylate (HEMA)is copolymerized with one of the prepolymers formed with polyethyleneglycol, use of toluene causes the HEMA to form heterogenous domainswhich are not stable under aggressive hydrolytic conditions.

Some of the preferred copolymers are polymerized from the followingcomonomer mixtures: Copolymer A Wt. % Component 80 prepolymer of thehard-soft-hard configuration made from 2-hydroxyethyl methacrylate,isophorone diisocyanate, neopentyl glycate and disilanol endcappedpolydimethylsiloxane of molecular weight equal to 3000 (INS3H) 202-hydroxyethylmethacrylate

Copolymer B 30-45 INS3H 40-55 tris(trimethylsiloxy)silylpropyl 15-25methacrylate N-N dimethylacrylamide

Copolymer C 30-90 prepolymer of the hard-soft-hard configuration madefrom hydroxyethylmethacrylate, isophorone diisocyanate 1,4-butanedioland disilanol endcapped polydimethylsiloxane of average molecular weightof about 3000 (IBS3H) or similar polysiloxane of about 4000 molecularweight (IBS4H) 10-40 dimethylacrylamide

Copolymer D 30-90 IBS4H or IBS3H 20-40 dimethylacrylamide  5-30tris(trimethylsiloxy)silyl propyl methacrylate

Copolymer E 30-90 prepolymer of the hard-soft-hard configuration madefrom 2-hydroxyethylmethacrylate, isophorone diisocyanate, diethyleneglycol, and the disilanol endcapped polydimethylsiloxane of molecularweight 3000 or 4000 (IDS3H and IDS4H, respectively) 20-40dimethylacrylamide  1-30 tris(trimethylsiloxy)silyl propyl methacrylate

Various homopolymers and copolymers films were formed and characterizedby standard testing procedures such as:

-   -   1. Tensile strength (g/mm²) and modulus of elasticity were        measured per ASTM test method D1708.    -   2. Elongation was measured per ASTM 1708.    -   3. Initial tear strength and propagation tear strength were        measured per ASTM 1438.    -   4. oxygen permeabilities were measured by the method reported by        Relojo, M. et al in Contact and Intraocular Lens Medical        Journal, Vol. 3, issued p. 27 (1977) and edge effects were        accounted for per the methods described by Fatt, et al. in        International Contact Lens Clinic, V. 14, p. 389 (1987).    -   5. Water content is measured per a gravimetric method.    -   6. Refractive index was measured per typical methods on hydrated        samples using a refractometer.

As mentioned, the prepolymers of the present invention are particularlyuseful in forming shaped articles used in biomedical applications. Thesepolymers and copolymers can be used to make biomedical devices i.e.shaped articles, such as dialyzer diaphragms, to prepare artificialkidneys and other biomedical implants, such as disclosed in Wichterle,U.S. Pat. No. 2,976,576 and Wichterle, U.S. Pat. No. 3,220,960. Theinstant polymers and copolymers can be used in preparing therapeuticbandages as disclosed in Shephard, U.S. Pat. No. 3,428,043. The instantpolymers and copolymers can also be used in preparing medical surgicaldevices e.g. heart valves, vessel substitutes, intra-uterine devices,membranes and other films, dialyzer diaphragms, catheters, mouth guards,denture liners and other such devices as disclosed in Shephard U.S. Pat.No. 3,520,949 and Shephard U.S. Pat. No. 3,618,231. The instant polymersand copolymers can be used to modify collagen to make blood vessels,urinary bladders and other such devices as disclosed in Kliment U.S.Pat. No. 3,563,925. The instant polymers and copolymers can be used tomake catheters as disclosed in Shephard U.S. Pat. No. 3,566,874. Theinstant polymers and copolymers can be used as semipermeable sheets fordialysis, artificial dentures and all of such disclosures as set forthin Stoy U.S. Pat. No. 3,607,848. The instant polymers and copolymers canbe used in ophthalmic prostheses and all other uses disclosed inWichterle U.S. Pat. No. 3,679,504. They may also be used as a polymericmatrix for controlled release of active pharmaceutical agents.

In the following examples, the properties of such films derived from theclaimed prepolymer and combinations of prepolymers with variouscomonomers are described. For certain comonomers which employed“hydrophilic” comonomers, the films were hydrated to “hydrogel”states-their physical properties were measured as hydrated. Thefollowing examples are meant to illustrate the invention, but do notdefine the final scope of the invention.

EXAMPLE 1 Synthesis of Hard-Soft-HARD Prepolymer Based onToluene-2.4-Diisocyanate

2 mole equivalents of toluene-2,4-diisocyanate (TDI) were dissolved intoluene with one mole equivalent hydrogenated bisphenol A (HBPA) in aresin kettle with constant stirring under nitrogen. This STAGE Areaction was run at 60-90° C. for 2-3 hours in the presence of 0.5 wt %“DABCO” catalyst.

One mole equivalent of polypropylene glycol with a molecular weight ofabout 1000 was then slowly added to the reaction mixture and reacted for2-3 hours at 60-80° C. under nitrogen.

Excess 2-hydroxyethyl methacrylate (HEMA) was added to the isocyanateterminated STAGE B reaction mixture and then reacted to completion.

Variations of the above synthesis were run by substitutingneopentylglycol (NPG) for the hydrogenated Bisphenol A, and bysubstituting various molecular weight polypropylene glycols for thePPG-1000.

The resulting prepolymers were homopolymerized between treated glassplates in the presence of a free radical catalyst, benzoin methylether.The polymerization was UV initiated in toluene. The solvent was removedby vacuum and the resultant films were characterized. The resultsobtained are reported in TABLE 1.

The oxygen permeability of the homopolymers increase as the molecularweight of the polypropylene glycol increased.

EXAMPLE 2 Hard-Soft-Hard Prepolymer Using Isophorone Diisocyanate (IPDI)

The same basic synthetic procedure as described in the previous examplewas employed except that, due to the decreased reactivity of isophoronediisocyanate relative to toluene diisocyanate, higher levels of reactioncatalyst were used. Reaction conditions and summary of the curedhomopolymer films is reported in TABLE 2.

Once again, the oxygen permeability of the cured prepolymer increasedwith increasing molecular weight of the polypropylene glycol polymer.These prepolymers did not produce yellowed films as the TDI materialsdid upon hydrolytic testing. TABLE 1 Catalyst Composition R_(X)TempSolvent (Dabco) O₂ Permeability (DK) TD1-NPG-PPG-1000-HEMA 45 methyleneA = 0 2 chloride B, C = 0.05 wt % TD1-NPG-PPG-2000-HEMA 45 methylene A =0 9 chloride/ B, C = 0.05 2 toluene TD1-NPG-PPG-3000-HEMA 45 toluene A =0 20 B, C = 0.05 TD1-NPG-PPG-4000-HEMA 45 2 toluene/ A = 0 30 1methylene B, C = 0.05 chloride TD1-HBPA-PPG-1000-HEMA A₁B = 75 toluene/A = 0 2 C = 60 methylene B, C = 0.05 chloride TD1-HBPA-PPG-2000-HEMA A₁B= 75 toluene/ A = 0 5 C = 60 methylene B, C = 0.05 chlorideTD1-HBPA-PPG-3000-HEMA A₁B = 75 toluene/ A = 0 15 C = 60 methylene B, C= 0.05 chloride TD1-HBPA-PPG-3000-HEMA A₁B = 75 toluene/ A = 0 25 C = 60methylene B, C = 0.05 chloride

TABLE 2 IPDI BASED HARD-SOFT-HARD FILMS Catalyst* Oxygen Contact Rx Temp(concen. %) Permeability Angle Composition Solvent A B C A B C (DK) (°)IPDI-NPG-PPG-1000-HEMA Toluene 80 80 50 0.25 0.25 0.25 3.4 53IPDI-NPG-PPG-2000-HEMA Toluene 80 80 60 0.5 0.5 0.5 13.8 35IPDI-NPG-PPG-3000-HEMA Toluene 80 80 60 0.5 0.5 0.5 24.3 42IPDI-NPG-PPG-4000-HEMA Toluene 75 85 50 0.25 0.25 0.25 33.2 41IPDI-CHDM-PPG-1000-HEMA Toluene 85 85 50 0.25 0.25 0.25 2.0 59IPDI-CHDM-PPG-2000-HEMA Toluene 85 85 45 0.5 0.25 0.25 10.9 43IPDI-CHDM-PPG-3000-HEMA Toluene 80 80 60 0.5 0.25 0.25 21.0 42IPDI-CHDM-PPG-4000-HEMA Toluene 85 85 50 0.25 0.25 0.25 30.1 41IPDI-HBPA-PPG-1000-HEMA Toluene 85 85 50 0.25 0.25 0.25 1.5 62IPDI-HBPA-PPG-2000-HEMA Toluene 85 85 45 0.25 0.5 0.5 8.0 41IPDI-HBPA-PPG-3000-HEMA Toluene 85 85 45 0.3 0.3 0.3 17.4 44IPDI-HBPA-PPG-4000-HEMA Toluene 80 80 50 0.25 0.25 0.25 24.1 44

EXAMPLE 3 4,4-Di-Cyclohexyl Methane Diisocyanate Based Hard-Soft-HardPrepolymers

Hard-soft-hard prepolymers were synthesized per the examples supraexcept that H₁₂-MDI was used. Films were cured from 300% prepolymersolution in toluene as reported in TABLE 3.

In general, the H₁₂-MDI prepolymers produced films with greater tearstrengths than the TDI or IPDI diisocyanate based systems and wereslightly less oxygen permeable.

EXAMPLE 4 Copolymers of IPDI Based Hard-Soft-Hard Prepolymers withHydrophilic Monomers

A hard-soft-hard prepolymer produced with isophorone diisocyanate(IPDI), neopentyl glycol (NPG), polypropylene glycol with a molecularweight of 4000 and 2-hydroxethyl methacrylate was copolymerized with ahydrophilic comonomer. Various copolymers of this prepolymer (INP4H)with various comonomers were made and tested.

The general scheme for making the copolymer involved mixing theprepolymer with the comonomer in a 30-70 wt % solution in toluene in thepresence of a known free radical catalyst. The solutions were placedbetween treated glass plates and polymerized. The films were thenphysically characterized. TABLE 3 H₁₂-MDI HARD-SOFT-HARD PREPOLYMERSTensile Contact Tear (P) Strength Modulus Elongation Composition Oxy(DK) Angle(°) (g/mm) (g/mm²) (g/mm²) (%) NPG PPG-1000 2.3 41 * 132.9 828170.1 PPG-2000 10.7 39 187 743.2 931.2 172.5 PPG-3000 20.4 33 91.8 514.5386.5 190.8 PPG-4000 29.3 39 108 201.5 185.1 218.2 CHDM PPG-1000 1.844 * 1282 16000 173.8 PPG-2000 8.4 41 437 612.7 1676 282.1 PPG-3000 18.638 290 399.9 373.2 348.7 PPG-4000 28.0 41 170 169.9 170 301.9 HBPAPPG-1000 1.2 62 * 2271 32610 84.6 PPG-2000 6.4 43 256 1160 3590 221.7PPG-3000 14.2 41 197 672.2 1607 217.5 PPG-4000 23.2 44 130 433.9 615.9198.6* too stiff to measure

Specific hydrophilic comonomers used were 2-hydroxethyl methacrylate andN-2-vinylpyrrolidinone. The characteristics of these copolymers isdisclosed in TABLE 4.

Several interesting features are displayed by the resultant films. Ingeneral, the contact angle of the material was lowered as the content ofhydrophilic comonomers increased, as did water content. However, oxygenpermeability decreased as the water content of the hydrated materialincreased. Normally, water content and O₂ permeability of hydrogelmaterials is directly related rather than inversely related.

EXAMPLE 5 Polymer Alloys of Polymerized Hard-Soft-Hard Materials

A homopolymer of INP4H was prepared and then soaked in a solution ofN-vinyl pyrrolidinone containing a free radical catalyst. The films werethen subjected to UV radiation in order to polymerize theN-vinylpyrrolidone. Based upon analysis of the extracted parties of thepolymerized polymer alloy, wt % of polymerized N-vinyl pyrrolidinonecould be calculated. The characteristics of these polymer alloys isreported in TABLE 5.

It was observed that these alloy materials felt much more slippery thanthe copolymers made from the same monomer combinations. TABLE 4 IPDIBASED HARD-SOFT-HARD/HYDROPHILIC COMONOMERS Water Contact Tear (p)Tensile Tensile Content O₂ Angle Strength Strength Modulus Elong.Copolymer Composition (%) (DK) (°) (g/mm) g/mm² g/mm² % INP4H:HEMA100:0  — 33.2 41 74.2 219.3 117.8 294 80:20 8.3 19.7 36 55.2 65.4 162285 60:40 19.4 13.3 38 31.0 97.4 91.1 258 40:60 26.5 10.4 37 13.0 58.880.0 155  0:100 38.6 9 — 4.2 56 57 225 INP4H:NVP 90:10 9.0 15.9 45 — — —— 80:20 17.7 24.4 37 15.1 55.8 71.4 243 60:40 43.7 25.7 35 5.3 77.7117.9 174 40:60 58.5 31.6 37 2.5 17.4 50.8 72.4

TABLE 5 POLYMER ALLOYS Water Contact Alloy Composition Content O₂ AngleINP4H: NVP (IPN) (%) (DK) (°) 96.6: 3.4 7.9 26.2 55 94.8 5.2 12.6 25.743 89.5 10.9 15.8 25.5 46 81.3 18.7 27.7 17.9 40 78.2 21.8 31.3 20.6 3974.8 25.2 38.7 22.9 38

EXAMPLE 6 Copolymers of Hard-Soft-Hard Prepolymer (INP4H) withFluoromonomers

In the interest of producing copolymers with less lipid uptake valuescertain fluorinated comonomers, octafluoropentyl methacrylate (OFPMA)and hexafluoro isopropyl methacrylates, (HFIPMA) were copolymerized withINP4H prepolymers in various ratios. The cured copolymer films arecharacterized in TABLE 6.

As the fluoro content of the copolymer was increased the oleic acidpickup decreased with a concomitant decrease in oxygen permeability. Thesamples with 80 wt % fluoromonomer content were too brittle tocharacterize.

EXAMPLE 7 Copolymers of INP4H with Silicone Monomers

Various copolymers were produced from combinations of INP4H withtris(trimethylsiloxy)silylpropyl methacrylate (referred to as tris) and2-hydroxyethyl methacrylate and characterized in TABLE 7.

These copolymers exhibit very good oxygen permeabilities and oleic aciduptake characteristics as well as vastly superior tear strengths andtensile moduli with respect to pHEMA. TABLE 6 COPOLYMERS OF INP4H WITHFLUORINATED COMONOMERS Elon- Contact Tear Tensile Tensile ga- O₂ AngleStrength Strength Modulus tion Composition (DK) (°) g/mm² g/mm² g/mm²(%) INP4H:OFPMA 80:20 23.9 40 107 238.1 254.6 225 60:40 20.8 45 155412.8 365.4 320 40:60 17.6 50 447 569.7 3020 318 20:80 — — — — — —INP4H:HGIPMA 80:20 28.0 40 269 405.9 615.2 263 60:40 24.8 42 235 10432408 383 40:60 21.3 44 — — — — 20:80 — — — — — —

TABLE 7 INP4H-TRIS-HEMA COPOLYMERS Copolymer Water Contact Oleic TearTensile Composition Content O₂ Angle Protein (dry (P) Modulus ElongINP4H:HEMA:Tris (%) Appear. (DK) (°) ug/mg film) % (g/mm) (g/mm²) (%)100:0:0 33.2 Clear 33.2 41 348 74.2 117.8 254  80:20:0 8.3 Clear 13.3 360 179 55.2 162 285  60:40:0 19.4 Clear 19.7 38 0 113 31.0 91.1 258 40:60:0 26.5 Hazy 10.4 37 0 43.6 13.0 80.0 155  0:100:0 38.6 Clear 9.0— 0-1 29.0 4.2 57.0 225  60:20:20 6.4 Clear 31.7 33 0 216 50.0 55.4 345 50:20:30 7.8 Clear 42.4 40 0 192 42.6 56.3 399  40:20:40 9.8 Clear 52.942 0 192.0 82.2 75.4 460  40:50:10 17.5 Hazy 15.9 32 0 62.5  40:40:2013.4 Clear 22.9 30 0 79.6  40:30:30 10.5 Clear 26.7 33 0 112  40:20:405.7 Clear 43.5 34 0 172

EXAMPLE 8 Hydrolytic Stability of INP4H/HEMA Copolymers

Hydrolytic stability testings of INPD4H/HEMA copolymers formed intoluene were conducted by subjecting the copolymeric samples to hostileaqueous conditions (either acidic or basic H₂O at elevated temperatures)for extended periods of up to 14 days. These copolymers showedconsistent and significant loss of mass during the hydrolytic testingwhich indicated that the copolymerization process was not efficient.

Chemical analysis of the extracted portion revealed that the portionbeing extracted was largely an oligomeric product of the 2-hydroxyethylmethacrylate.

Subsequently, INP4H/HEMA/TRIS copolymers were produced without aid of asolvent. These copolymers proved to be hydrolytically stable under thesame conditions as the toluene solution produced polymers had beentreated under.

EXAMPLE 9 Synthesis of Hard-Soft-Hard Prepolymers using PolysiloxaneDiols and Copolymers Thereof

α, ω-bis(hydroxybutyldimethylsily) polysiloxane was prepared by reactingdimethoxydimethylsilane with1,3-bis(4-hydroxybutyl)tetramethyldisiloxane in water under acidicconditions. The average molecular weight of the polymer was about 3100.Using the general synthetic scheme for hard-soft-hard prepolymers withthe above long chain diol, isophorone diisocyanate (IPDI),neopentylglycol (NPG) and 2-hydroxyethyl methacrylate end blocker(HEMA), a prepolymer was formed (INS3H).

This prepolymer was copolymerized with 2-hydroxyethyl methacrylate invarious ratios. The characteristics of these copolymers is reported inTABLE 8.

These films were all hydrolytically stable.

EXAMPLE 10 Terpolymers of INP4H Prepolymers

Terpolymers of INP4H/TRIS/glycerol methacrylate (GM) andINP4H/TRIS/N—N-dimethylacrylamide (DMM) were prepared and evaluated. Thecharacteristics of these films is summarized in TABLES 9A and 9B.

These terpolymers provide soft hydrogel type materials with excellentoxygen permeability and physical strength characteristics. TABLE 9B O₂INP4H:TRIS:DMA DK 30:50:20 80 25:50:25 75

TABLE 8 INS3H/HEMA COPOLYMERS Composition O₂ INS3H:HEMA (DK) % H₂OModulus Elongation Tear 80:20 262 5 6600 140 10 70:30 189 9 4500 170 1260:40 112 13 1800 160 80

TABLE 9A INP4H:TRIS:GM TERPOLYMERS Formulation Contact INP4H:TRIS:GM O₂(DK) Angle (°) % H₂O Tensile Modulus Strength Tear 30:50:20 78 48 14 6294 380 83 25:50:25 86 — 11 82 370 300 90 20:50:30 62 — 17 96 250 170 45

EXAMPLE 11 Hard-Soft-Hard Urethane Silicone Prepolymers with “Softer”Hard Portions

Siloxane containing prepolymers were produced as before except 1,4butanediol or diethyleneglycol was used in place of neopentyl glycol. Ingeneral, the homopolymers and copolymers of these materials had lowermodulis and tear strengths than their neopentyl glycol basedcounterparts.

IBS4H Prepolymer is formed using the general scheme for hard-soft-hardprepolymers using isophorone diisocyanate, 1,4-butanediol, the α,ω-hydroxyalkyl endcapped polydimethylsiloxane described earlier with amolecular weight of about 4000, and 2-hydroxyethyl methacrylate.

IBS3H Prepolymer is the same prepolymer as IBS4H except with a lowermolecular weight polydimethylsiloxane. IDS4H and IDS3H are equivalent toIBS4H and IBS3H, respectively, except diethyleneglycol was used in placeof 1,4 butanedial.

The physical characteristics of copolymers formed from these prepolymerswith dimethylacrylamide (DMA) and/or tris (trimethylsiloxy)silyl propylmethacrylate are reported in TABLE 10. All of the prepolymers werehydrolytically stable.

EXAMPLE 12 Soft-Hard-Soft Prepolymers

According to the general scheme for producing soft-hard-soft prepolymerswere formed using 2-hydroxyethyl-methacrylate TABLE 10 HARD-SOFT-HARDSILICONE PREPOLYMERS O₂ Contact Tensile Modulus Tear Formulation (DK)Water % Angle (°) (g/mm²) (g/mm²) Elongation % (g/mm²) IBS3H:DMA 100:0399.3 0 — 347.4 1242 70.4 28.2  70:30 110.4 55 124.0 531.0 70.5 13.2 60:40 49.2 59 75.6 239.2 62.1 6.4 IBS4H:DMA 100:0 146.8 193.7 574.982.7 11.1  70:30 126.5 57.2 186.5 53.3 5.0  60:40 71.7 38.2 49.1 155.652.3 3.4 IDS3H:DMA:Tris 100:0:0 478.8 — 480.3 2861 56.1 36.9  70:30:067.0 26.4 65.2 220.5 45.0 3.8  60:30:10 60.1 31.1 55.7 169.2 53.5 4.9 50:30:20 45.6 40.6 48.9 140.5 56.9 2.4  40:30:30 113.1 22.4 59.5 79.8133.8 15.1  60:40 36.4 38.9 58.0 223.4 37.4 2.4 IDS4H:DMA:Tris 100:0:074.2 602.7 1141 41.4 —  70:30 120.4 52.1 175.6 46.5 2.4  60:30:0 76.429.2 42.7 116.5 59.0 2.7  50:30:20 113.4 28.2 34.9 68.5 88.2 4.8  60:4067.0 43.6 173.8 34.8 2.5(HEMA), isophorone diisocyanate (IPDI), neopentyl glycol (NPG) and adisilanol endcapped polydimethysiloxane with an average molecular weightof about 1500 (Si-1500). The general chemical structure of theprepolymer wasHEMA-IPDI-Si-1500-IPDI-NPG-IPDI-Si-1500-HEMA

Copolymers of the above prepolymer were formed withN—N-Dimethylacrylamide and tris(trimethylsiloxy)silyl-propylmethacrylateas reported in TABLE 11.

COMPARATIVE EXAMPLE Soft Segment Prepolymer

To illustrate the beneficial properties of the invention a comparativeprepolymer was formed from 2-hydroxyethyl methacrylate (HEMA),isophorone diisocyanate (IPDI) and an α, ω-dihydroxyalkyl endcappedpolydimethyl siloxane with an average molecular weight of about 3000(Si-3000). The structure of the prepolymer wasHEMA-IPDI-Si-3000-IPDI-HEMA

Copolymers of this prepolymer with N—N-dimethyl acrylamide andtris(trimethylsiloxy)silylpropyl-methacrylate are characterized in TABLE12.

These copolymers displayed much lower tear, modulus and tensile strengththan the copolymers of the present invention. TABLE 11 SOFT-HARD-SOFTPREPOLYMERS Formulation Contact Tensile Modulus Tear Prepolymer/DMA/Tris(DK) % Water Angle (°) g/mm² g/mm² Elongation % g/mm 100/0/0 283 — — 604500 164 70  70/30/0 114 25.7 51 111 350 70 35  35/30/35 114 23.8 52 84140 150 35  40/30/30 99 24.3 — 63 100 130 35

TABLE 12 COMPARATIVE SOFT SEGMENT PREPOLYMER Formulation Contact TensileModulus Tear Prepolymer/DMA (DK) % Water Angle (°) g/mm² g/mm²Elongation % g/mm 100:0: 624 0 — 195 620 53 9  70:30: 158 25 — 56 250 303

1. A prepolymer material described by the general chemical formulaeE(*D*A*D*G)_(a)*D*A*D*E′ orE(*D*G*D*A)_(a)*D*G*D*E′ where A denotes a divalent polymeric radicalchosen from the group of

wherein R^(P) denotes a straight or branched alkyl group with 1 to 6carbon atoms and n provides for a moiety weight of the radical between2000 and 10,000; R^(F) denotes a fluorinated straight or branched alkylradical with 1 to 6 carbon atoms and m provides a moiety weight ofbetween 400 and 10,000; R^(S) denotes an alkyl radical or a short chainfluorinated alkyl radical with 1 to 3 carbon atoms; and p provides amoiety weight of 400 to 10,000; D denotes an alkyl diradical, an alkylcycloalkyl diradical, a cycloalkyl diradical, an alkylaryl diradical oran aryl diradical, with 6 to 30 carbon atoms; G denotes an alkyldiradical, a cycloalkyl diradical, an alkyl cycloalkyl diradical, anaromatic diradical or an alkylaromatic diradical with 1 to 40 carbonatoms which may have ether, thio, or amine linkages in the main chain; *denotes a urethane or ureido linkage; and E and E′ denote polymerizableunsaturated organic radicals represented by the general chemical formula

wherein R¹ denotes a divalent alkylene radical with 1 to 10 carbonatoms; R² denotes a —H or —CH₃ radical; R³ denotes a —H radical or analkyl radical with 1 to 6 carbon atoms or a

radical where Y is —O—, —S— or —NH— and R⁴ denotes an alkyl radical with1 to 12 carbon atoms; X denotes

Ar denotes an aromatic radical with 6 to 30 carbon atoms; a is at least1; w is 0 to 6; x is 0 or 1; y is 0 or 1; and z is 0 or
 1. 2. Theprepolymer of claim 1 wherein the polymeric radical, A, is apolyethylene radical with a molecular weight of at least about
 2000. 3.The prepolymer of claim 2 wherein the D radical is formed from the groupof diisocyanates consisting of isophorone diisocyanate, toluenediisocyanate and H₁₂-methylene diisocyanate.
 4. The prepolymer of claim3 wherein the G radical is formed from the group of diols consisting ofneopentylglycol, 1,4-butanediol, diethyleneglycol and triethyleneglycol.
 5. The prepolymer of claim 1 wherein the polymeric radical, A,is a dialkyl endcapped polydimethylsiloxane radical with a molecularweight of at least
 400. 6. The prepolymer of claim 5 wherein the Dradical is formed from the group of diisocyanate consisting ofisophorone diisocyanate, toluene diisocyanate, and H₁₂-methylenediisocyanate.
 7. The prepolymer of claim 6 wherein the G radical isformed from the group of diols consisting of neopentylglycol,1,4-butanediol, diethylene glycol and triethylene glycol.
 8. Theprepolymer of claim 1 wherein the polymeric radical, A, is a dialkylendcapped polydifluoroalkyl-siloxane polymer with a molecular weight ofat least
 400. 9. The prepolymer of claim 8 wherein the D radical isformed from the group of diisocyanates consisting of isophoronediisocyanate, toluene diisocyanate, and H₁₂-methylene diisocyanate. 10.The prepolymer of claim 9 wherein the G radical is formed from the groupof diols consisting of neopentyl glycol, 1,4-butanediol, diethyleneglycol and triethylene glycol.
 11. The prepolymer of claim 1 wherein thepolymeric radical, A, is a fluoroalkyl ether with a molecular weight ofat least about
 400. 12. The prepolymer of claim 11 wherein the D radicalis formed from the group of diisocyanates consisting of isophoronediisocyanate, toluene diisocyanate and H₁₂-methylene diisocyanate. 13.The prepolymer of claim 11 wherein the G radical is formed from thegroup of diols consisting of neopentyl glycol, 1,4-butanediol,diethylene glycol and triethylene glycol.
 14. A copolymer materialformed by polymerizing a comonomer mixture comprised of: (I) theprepolymer described by the general chemical formulaeE(*D*A*D*G)_(a)*D*A*D*E′ orE(*D*G*D*A)_(a)*D*G*D*E′ where A denotes a divalent polymeric radicalchosen from the group of

wherein R^(P) denotes a straight or branched alkyl group with 1 to 6carbon atoms and n provides for a moiety weight of the radical between2000 and 10,000; R^(F) denotes a fluorinated straight or branched alkylradical with 1 to 6 carbon atoms and m provides a moiety weight ofbetween 400 and 10,000; R^(S) denotes an alkyl radical or a short chainfluorinated alkyl radical with 1 to 3 carbon atoms; and p provides amoiety weight of 400 to 10,000; D denotes an alkyl diradical, an alkylcycloalkyl diradical, a cycloalkyl diradical, an alkylaryl diradical oran aryl diradical, with 6 to 30 carbon atoms; G denotes an alkyldiradical, a cycloalkyl diradical, an alkyl cycloalkyl diradical, anaromatic diradical or an alkylaromatic diradical with 1 to 40 carbonatoms; * denotes a urethane or ureido linkage; and E and E′ denotepolymerizable unsaturated organic radicals represented by the generalchemical formula:

wherein R¹ denotes a divalent alkylene radical with 1 to 10 carbon atomsR² denotes a —H or —CH₃ radical; R³ denotes a —H radical or an alkylradical with 1 to 6 carbon atoms or a

radical where Y is —O—, —S— or —NH—; and R⁴ denotes an alkyl radicalwith 1 to 12 carbon atoms; X denotes

Ar denotes an aromatic radical with 6 to 30 carbon atoms; a is at leastL; w is 0 to 6; x is 0 or 1; y is 0 or 1; z is 0 or 1; and (II) ahydrophilic comonomer.
 15. The copolymer of claim 14 wherein thepolymeric radical of component (I), A, is polyethylene radical with amolecular weight of at least about
 2000. 16. The copolymer of claim 15wherein component (I) comprises 15 to 95 weight percent of the comonomermixture and said hydrophilic monomer comprises 5 to 85 weight percent ofsaid comonomer mixture.
 17. The copolymer of claim 16 which furthercomprises a diethylenically reactive crosslinker.
 18. The copolymer ofclaim 17 wherein said hydrophilic monomer is chosen from the group ofhydrophilic monomers consisting of 2-hydroxyethyl methacrylate,N-vinyl-2-pyrrolidinone, methacrylic acid, dimethyl acrylamide, andglycerol methacrylate.
 19. The copolymer of claim 14 wherein thepolymeric radical of component (I), A, is a dialkyl endcappedpolydimethylsiloxane radical with a molecular weight of at least 400.20. The copolymer of claim 19 wherein component (I) comprises 15 to 95weight percent of the comonomer mixture and said hydrophilic comonomercomprises 5 to 85 weight percent of said comonomer mixture.
 21. Thecopolymer of claim 20 wherein said hydrophilic comonomer is chosen fromthe group consisting of 2-hydroxy-ethyl methacrylate,N-vinyl-2-pyrrolidinone, methacrylic acid, dimethyl acrylamide andglycerol methacrylate.
 22. The copolymer of claim 21 which furthercomprises 5 to 40 weight percent organosilicon comonomer.
 23. Thecopolymer of claim 14 wherein the polymeric radical of component (I), A,is a poly(fluoroalkyl)ether with a molecular weight of at least
 400. 24.A copolymer formed by polymerizing a comonomer mixture comprised of: (I)the prepolymer described by the general chemical formulaeE(*D*A*D*G)_(a)*D*A*D*E′ orE(*D*G*D*A)_(a)*D*G*D*E′ where A denotes a divalent polymeric radicalchosen from the group of

wherein R^(P) denotes a straight or branched alkyl group with 1 to 6carbon atoms and n provides for a moiety weight of the radical between2000 and 10,000; R^(F) denotes a fluorinated straight or branched alkylradical with 1 to 6 carbon atoms and m provides a moiety weight ofbetween 400 and 10,000; R^(S) denotes an alkyl radical or a short chainfluorinated alkyl radical with 1 to 3 carbon atoms; and p provides amoiety weight of 400 to 10,000; D denotes an alkyl diradical, an alkylcycloalkyl diradical, a cycloalkyl diradical, an alkylaryl diradical oran aryl diradical, with 6 to 30 carbon atoms; G denotes an alkyldiradical, a cycloalkyl diradical, an alkyl cycloalkyl diradical, anaromatic diradical or an alkylaromatic diradical with 1 to 40 carbonatoms; * denotes a urethane or ureido linkage; and E and E′ denotepolymerizable unsaturated organic radicals represented by the generalchemical formula:

wherein R¹ denotes a divalent alkylene radical with 1 to 10 carbon atomsR² denotes a —H or —CH₃ radical; R³ denotes a —H radical or an alkylradical with 1 to 6 carbon atoms or a

radical where Y is —O—, —S— or —NH—; and R⁴ denotes an alkyl radicalwith 1 to 12 carbon atoms; X denotes

Ar denotes an aromatic radical with 6 to 30 carbon atoms; a is at least1; w is 0 to 6; x is 0 or 1; y is 0 or 1; z is 0 or 1; and (II) ahydrophilic comonomer.
 25. The copolymer of claim 24 wherein saidorganosilicon monomer is tris(trimethylsiloxy)silyl-propyl methacrylate.26. The copolymer of claim 25 which comprises 20-50 wt % prepolymer (I),20-40 weight percent tris(trimethylsiloxy)-silyl propyl methacrylate.27. The copolymer of claim 26 which further comprises 10-35 weightpercent of the hydrophilic comonomer, dimethylacrylamide.
 28. Thecopolymer of claim 26 which further comprises from 10-35 weight percentof the hydrophilic comonomer glycerol methacrylate.
 29. The copolymer ofclaim 26 which further comprises from 10-35 weight percent of thehydrophilic comonomer 2-hydroxyethyl methacrylate.
 30. The copolymer ofclaim 26 which further comprises from 10-35 weight percent of thehydrophilic monomer N-vinyl-2-pyrrolidinone.
 31. A copolymer formed bypolymerizing a comonomer mixture comprised of: (I) the prepolymerdescribed by the general chemical formulaeE(*D*A*D*G)_(a)*D*A*D*E′ orE(*D*G*D*A)_(a)*D*G*D*E′ where A denotes a divalent polymeric radicalchosen from the group of

wherein R^(P) denotes a straight or branched alkyl group with 1 to 6carbon atoms and n provides for a moiety weight of the radical between2000 and 10,000; R^(F) denotes a fluorinated straight or branched alkylradical with 1 to 6 carbon atoms and m provides a moiety weight ofbetween 400 and 10,000; R^(S) denotes an alkyl radical or a short chainfluorinated alkyl radical with 1 to 3 carbon atoms; and p provides amoiety weight of 400 to 10,000; D denotes an alkyl diradical, an alkylcycloalkyl diradical, a cycloalkyl diradical, an alkylaryl diradical oran aryl diradical, with 6 to 30 carbon atoms; G denotes an alkyldiradical, a cycloalkyl diradical, an alkyl cycloalkyl diradical, anaromatic diradical or an alkylaromatic diradical with 1 to 40 carbonatoms; * denotes a urethane or ureido linkage; and E and E′ denotepolymerizable unsaturated organic radicals represented by the generalchemical formula:

wherein R¹ denotes a divalent alkylene radical with 1 to 10 carbon atomsR² denotes a —H or —CH₃ radical; R³ denotes a —H radical or an alkylradical with 1 to 6 carbon atoms or a

radical where Y is —O—, —S— or —NH—; and R⁴ denotes an alkyl radicalwith 1 to 12 carbon atoms; X denotes

Ar denotes an aromatic radical with 6 to 30 carbon atoms; a is at leastI; w is 0 to 6; x is 0 or 1; y is 0 or 1; z is 0 or 1; and (II) afluoroorgano comonomer.
 32. A biomedical device made from a polymercomprising the prepolymer of claim 1.